The macrophage inhibitory cytokine-1 (MIC-1), also known as GDF-15 and placental bone morphogenetic protein (PLAB), is a distant member of the TGF-beta super family, a family of peptide hormones involved in cell growth and differentiation. MIC-1 circulates as a cysteine-rich homodimer with a molecular mass of 24.5 kDa. MIC-1 was initially reported to be up-regulated in macrophages by stimuli including IL-1b, TNF-alpha, IL-2, and TGF-b. It was also shown that MIC-1 could reduce lipopolysaccharide-induced TNF-alpha production and it was based on these data proposed that MIC-1 was an anti-inflammatory cytokine. More recently, a study was investigating why human patients with advanced cancer were losing body weight and they showed that the weight loss correlated with circulating levels of MIC-1. These data indicates that MIC-1 regulates body weight. This hypothesis was tested in mice xenografted with prostate tumor cells, where data showed that elevated MIC-1 levels were associated with loss of body weight and decreased food intake, this effect being reversed by administration of antibodies to MIC-1. As administration of recombinant MIC-1 to mice regulated hypothalamic neuropeptide Y and pro-opiomelanocortin it was proposed that MIC-1 regulates food intake by a central mechanism. Furthermore, transgenic mice overexpressing MIC-1 are gaining less weight and body fat both on a normal low fat diet and on a high fat diet. Also, transgenic mice overexpressing MIC-1 fed both on a low and high fat diet, respectively, had improved glucose tolerance compared with wild type animals on a comparable diet.
Native MIC-1 has a short half-life, meaning that treatment with native MIC-1 requires daily administration to maintain efficacy.
WO 2001079443 concerns the use of human serum albumin or variants thereof for fusions to peptides of pharmaceutical interest.
WO 2005099746 concerns a method of modulating appetite and/or body weight by administering a MIC-1 modulating agent.